Tubuloglomerular feedback and tubular reabsorption during acute potassium loading in rats

1994 ◽  
Vol 267 (2) ◽  
pp. F223-F230 ◽  
Author(s):  
B. Braam ◽  
P. Boer ◽  
H. A. Koomans
Keyword(s):  
Distal Tubule ◽  
Plasma Potassium ◽  
Tubuloglomerular Feedback ◽  
Control Group ◽  
Sprague Dawley ◽  
Time Control ◽  
Sprague Dawley Rats ◽  
Single Nephron ◽  
Flow Pressure ◽  
Potassium Loading

Acute hyperkalemia has been associated with changes in reabsorption, glomerular filtration rate (GFR), and autoregulation, which might represent altered tubuloglomerular feedback (TGF) responsiveness. Therefore, TGF responsiveness, segmental reabsorption of water, sodium and potassium, and single-nephron GFR were evaluated during acute potassium loading in male Sprague-Dawley rats. Rats receiving 300 mM KNO3, KHCO3, and KCl showed significantly increased plasma potassium levels and attenuation of stop-flow pressure responses 45-90 min after starting the potassium infusion compared with that observed in time controls and rats infused with 300 mM NaCl. Attenuation of TGF responsiveness could not be related to plasma and kidney angiotensin II levels. Segmental water and sodium handling and proximal to distal single-nephron GFR differences assessed in a time control group and a group receiving 300 mM KCl revealed no changes related to KCl infusion. However, late proximal and early distal potassium concentrations increased significantly from 4.7 +/- 0.2 to 6.3 +/- 0.3 mM (P < 0.01) and from 1.5 +/- 0.1 to 2.7 +/- 0.4 mM (P < 0.01), respectively. In summary, although attenuated TGF responsiveness was demonstrated at higher perfusion rates, this study does not support a significant role for either the TGF mechanism or changes in reabsorption upstream of the early distal tubule for the initiation of kaliuresis during acute potassium loading.

Micropuncture analysis of single-nephron function in NHE3-deficient mice

1999 ◽  
Vol 277 (3) ◽  
pp. F447-F453 ◽  
Author(s):  
John N. Lorenz ◽  
Patrick J. Schultheis ◽  
Timothy Traynor ◽  
Gary E. Shull ◽  
Jürgen Schnermann
Keyword(s):  
Proximal Tubule ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Transport Processes ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Fluid Reabsorption ◽  
Fluid Delivery ◽  
Single Nephron ◽  
Flow Pressure

The Na/H exchanger isoform 3 (NHE3) is expressed in the proximal tubule and thick ascending limb and contributes to the reabsorption of fluid and electrolytes in these segments. The contribution of NHE3 to fluid reabsorption was assessed by micropuncture in homozygous ( Nhe3 −/−) and heterozygous ( Nhe3 +/−) knockout mice, and in their wild-type (WT, Nhe3 +/+) littermates. Arterial pressure was lower in the Nhe3 −/−mice (89 ± 6 mmHg) compared with Nhe3 +/+ (118 ± 4) and Nhe3 +/−(108 ± 5). Collections from proximal and distal tubules demonstrated that proximal fluid reabsorption was blunted in both Nhe3 +/− and Nhe3 −/−mice (WT, 4.2 ± 0.3; Nhe3 +/−, 3.4 ± 0.2; and Nhe3 −/−, 2.6 ± 0.3 nl/min; P < 0.05). However, distal delivery of fluid was not different among the three groups of mice (WT, 3.3 ± 0.4 nl/min; Nhe3 +/−, 3.3 ± 0.2 nl/min; and Nhe3 −/−, 3.0 ± 0.4 nl/min; P < 0.05). In Nhe3 −/−mice, this compensation was largely attributable to decreased single-nephron glomerular filtration rate (SNGFR): 10.7 ± 0.9 nl/min in the Nhe3 +/+ vs. 6.6 ± 0.8 nl/min in the Nhe3 −/−, measured distally. Proximal-distal SNGFR differences in Nhe3 −/−mice indicated that much of the decrease in SNGFR was due to activation of tubuloglomerular feedback (TGF), and measurements of stop-flow pressure confirmed that TGF is intact in Nhe3 −/−animals. In contrast to Nhe3 −/−mice, normalization of early distal flow rate in Nhe3 +/−mice was not related to decreased SNGFR (9.9 ± 0.7 nl/min), but rather, to increased fluid reabsorption in the loop segment ( Nhe3 +/+, 2.6 ± 0.2; Nhe3 +/−, 3.6 ± 0.5 nl/min). We conclude that NHE3 is a major Na/H exchanger isoform mediating Na+ and fluid reabsorption in the proximal tubule. In animals with NHE3 deficiency, normalization of fluid delivery to the distal tubule is achieved through alterations in filtration rate and/or downstream transport processes.

scholarly journals Testosterone enhances tubuloglomerular feedback by increasing superoxide production in the macula densa

2013 ◽  
Vol 304 (9) ◽  
pp. R726-R733 ◽  
Author(s):  
Yiling Fu ◽  
Yan Lu ◽  
Eddie Y. Liu ◽  
Xiaolong Zhu ◽  
Gouri J. Mahajan ◽  
...  
Keyword(s):  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Mediated Effects ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Laser Capture ◽  
Stop Flow ◽  
Dependent Pathway

Males have higher prevalence of hypertension and renal injury than females, which may be attributed in part to androgen-mediated effects on renal hemodynamics. Tubuloglomerular feedback (TGF) is an important mechanism in control of renal microcirculation. The present study examines the role of testosterone in the regulation of TGF responses. TGF was measured by micropuncture (change of stop-flow pressure, ΔPsf) in castrated Sprague-Dawley rats. The addition of testosterone (10−7 mol/l) into the lumen increased the ΔPsf from 10.1 ± 1.2 to 12.2 ± 1.2 mmHg. To determine whether androgen receptors (AR) are involved, mRNA of AR was measured in the macula dense cells isolated by laser capture microdissection from kidneys, and a macula densa-like cell line (MMDD1). AR mRNA was expressed in the macula densa of rats and in MMDD1 cells. We next examined the effects of the AR blocker, flutamide (10−5 mol/l) on the TGF response. The addition of flutamide blocked the effects of testosterone on TGF. The addition of Tempol (10−4 mol/l) or polyethylene glycol-superoxide dismutase (100 U/ml) to scavenge superoxide blocked the effect of testosterone to augment TGF. We then applied apocynin to inhibit NAD(P)H oxidase and oxypurinol to inhibit xanthine oxidase and found the testosterone-induced augmentation of TGF was blocked. In additional experiments in MMDD1 cells, we found that testosterone increased O2− generation. Apocynin or oxypurinol blocked the testosterone-induced increases of O2−, while blockade of COX-2 with NS-398 had no effect. These findings suggest that testosterone enhances TGF response by stimulating O2− production in macula densa via an AR-dependent pathway.

Tubuloglomerular feedback responses in the rat during calmodulin inhibition

1986 ◽  
Vol 250 (4) ◽  
pp. F715-F719 ◽  
Author(s):  
P. D. Bell
Keyword(s):  
Distal Tubule ◽  
Cytosolic Calcium ◽  
Ringer Solution ◽  
Tubuloglomerular Feedback ◽  
Calmodulin Antagonists ◽  
Vascular Elements ◽  
Recovery Times ◽  
Single Nephron ◽  
Flow Pressure ◽  
Feedback Responses

Previously, we have suggested that a cytosolic calcium system participates in the transmission of signals between distal tubular fluid and the glomerular vascular elements. Since the Ca-binding protein calmodulin has been implicated in the intracellular actions of cytosolic Ca, we evaluated the effects of the calmodulin antagonists trifluoperazine (TFP) and calmidazolium (R24571) on tubuloglomerular feedback responses. In the rat, stop-flow pressure (SFP) was measured during retrograde perfusion into the distal tubule at 15 nl/min for 5 min. Perfusion with an isotonic Ringer solution resulted in a decrease in SFP of 12 +/- 1.1 mmHg (n = 34). With the addition of 50-75 microM TFP, SFP was decreased by 11 +/- 1.0 mmHg (n = 24); with 500 microM TFP, SFP feedback responses were 10 +/- 1.2 mmHg (n = 7). During perfusion with 20 microM R24571, SFP decreased by an average of 12 +/- 1.1 mmHg (n = 18). Single-nephron glomerular filtration rate feedback responses during retrograde microperfusion were also unaltered by R24571 (delta 15 +/- 2.5 vs. delta 14 +/- 2.6 nl/min). In the SFP experiments it was observed that the recovery of SFP toward preinfusion values after cessation of perfusion was significantly prolonged in tubules perfused with the calmodulin antagonists. SFP recovery times averaged 65 +/- 5.5 s (control), 104 +/- 9.9 s (50-75 microM TFP), 154 +/- 9.6 s (500 microM TFP), and 116 +/- 9.9 s (20 microM R24571). Accordingly, these results suggest that activation of calmodulin is not required for the transmission of tubuloglomerular feedback signals.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Nitric oxide release as an essential mitigating step in tubuloglomerular feedback: observations during intrarenal nitric oxide clamp.

1998 ◽  
Vol 9 (9) ◽  
pp. 1596-1603
Author(s):  
E Turkstra ◽  
B Braam ◽  
H A Koomans
Keyword(s):  
Nitric Oxide ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Arginine Infusion ◽  
Nitric Oxide Release ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Oxide Synthase ◽  
Nitroprusside Infusion

Nitric oxide synthase inhibition in the kidney enhances tubuloglomerular feedback (TGF) responsiveness. This may reflect either the effect of reduced basal nitric oxide (NO) availability or the effect of impaired NO release that is physiologically induced by TGF activation. However, it is unknown whether the latter actually takes place. In this study, it was hypothesized that NO is released (from macula densa cells or endothelium) as part of the normal TGF loop, and mitigates the TGF response. In Sprague Dawley rats, TGF responsiveness was assessed (fall in tubular stop flow pressure, deltaSFP, upon switching loop of Henle perfusion rates from 0 to 40 nl/min) during an intrarenal NO clamp (systemic infusion of nitro-L-arginine, 10 microg/kg per min, followed by intrarenal nitroprusside infusion adjusted to restore renal blood flow [RBF]). This maneuver was presumed to fix intrarenal NO impact at a physiologic level. To validate the approach, TGF responsiveness during an intrarenal angiotensin II (AngII) clamp (systemic infusion of enalaprilat 0.2 mg/kg per min, followed by intrarenal AngII infusion) was also studied. AngII is presumed to modulate but not mediate, TGF, thus not to increase as part of the TGF loop. In untreated animals, RBF was 7.4 +/- 0.4 ml/min, and deltaSFP was 5.7 +/- 1.6 mmHg. Nitro-L-arginine infusion alone reduced RBF to 5.3 +/- 0.5 ml/min (P < 0.05); with nitroprusside infusion, RBF was restored to 8.3 +/- 0.7 ml/min. In this condition (NO clamp), deltaSFP was markedly increased to 19.6 +/- 3.2 mmHg (P < 0.05). By contrast, deltaSFP, which was virtually abolished during enalaprilat alone (0.2 +/- 0.3 mmHg), was not significantly different from controls during AngII clamp (8.2 +/- 1.0 mmHg). These data suggest that NO may well be released upon TGF activation. By contrast, AngII is not dynamically involved in TGF activation, but may modulate the TGF response. Thus, dynamic release of NO during TGF activation mitigates the TGF response, so that it will offset the action of a primary, as yet undefined, vasoconstrictor mediator. The source of this NO, macula densa or endothelium, remains to be elucidated.

scholarly journals Adenosine A2 receptors modulate tubuloglomerular feedback

2010 ◽  
Vol 299 (2) ◽  
pp. F412-F417 ◽  
Author(s):  
Mattias Carlström ◽  
Christopher S. Wilcox ◽  
William J. Welch
Keyword(s):  
Receptor Antagonist ◽  
Low Dose ◽  
Tubuloglomerular Feedback ◽  
High Dose ◽  
Sprague Dawley ◽  
Simultaneous Application ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Stop Flow ◽  
A2 Receptors

Adenosine can mediate the tubuloglomerular (TGF) response via activation of A1 receptors on the afferent arteriole, but both adenosine A1 and A2 receptors can regulate preglomerular resistance. We tested the hypothesis that adenosine A2 receptors offset the effect of A1 receptors and modulate the TGF. Maximal TGF responses were measured in male Sprague-Dawley rats as changes in proximal stop-flow pressure (ΔPSF) in response to increased perfusion of the loop of Henle (0 to 40 nl/min) with artificial tubular fluid (ATF). The maximal TGF response was studied after 5 min of intratubular perfusion (10 nl/min) with ATF alone, or with ATF plus the A2A receptor antagonist (ZM-241385; 10−7 or 10−5 mol/l), A1 receptor antagonist (PSB-36; 10−8 mol/l), or with a combination of A1 (PSB-36; 10−8 mol/l) and A2A (ZM-241385; 10−7 mol/l) antagonists. The maximal TGF response (ΔPSF) with ATF alone was 11.7 ± 1.0 mmHg. Specific A2 inhibition (low dose) enhanced the maximal TGF response (15.7 ± 0.8 mmHg; P < 0.01), whereas a high dose (unspecific inhibition) attenuated the response (5.0 ± 0.4 mmHg; P < 0.001). A1 inhibition alone led to a paradoxical TGF response, with an increase in PSF of 3.1 ± 0.5 mmHg ( P < 0.05). Simultaneous application of A1 and A2 antagonists abolished the TGF response (ΔPSF: 0.4 ± 0.3 mmHg). In conclusion, adenosine A2 receptors modulate the TGF response by counteracting the effects of adenosine A1 receptors.

Quantitative characterization of the tubuloglomerular feedback response: effect of growth

1984 ◽  
Vol 247 (5) ◽  
pp. F808-F815 ◽  
Author(s):  
J. P. Briggs ◽  
G. Schubert ◽  
J. Schnermann
Keyword(s):  
Flow Rate ◽  
Tubuloglomerular Feedback ◽  
Loop Of Henle ◽  
Sprague Dawley ◽  
Maximum Slope ◽  
Sprague Dawley Rats ◽  
Single Nephron ◽  
Renal Micropuncture ◽  
The Right

Studies were performed to characterize quantitatively the effect of changing loop of Henle flow rate on single nephron glomerular filtration rate (SNGFR) in male Sprague-Dawley rats of varying body weight. Rats weighing 100, 220, and 350 g were studied using standard renal micropuncture techniques. The relationship between loop of Henle flow rate (VLP) and SNGFR was characterized for individual nephrons by multiple determinations of SNGFR during loop perfusion. An inverse sigmoidal relationship was observed that could be described as delta SNGFR = a/(1 + ek(b-VLP], where delta SNGFR is the change in SNGFR from the value measured at zero loop flow, a is delta SNGFRmax, the maximum change, b is V1/2, the flow rate at which the response is half maximum, and k is [4f' (V1/2)]/a with f' (V1/2) the slope at V1/2. delta SNGFRmax increased with increasing body size (7.9 +/- 1.16, 18.9 +/- 0.90, and 25.2 +/- 2.73 nl/min, respectively, in the three groups), and the curve shifted to the right (V1/2 = 10.3 +/- 0.8, 15.4 +/- 0.83, and 22.3 +/- 1.22 nl/min). The maximum slope increased (f' (V1/2) = 0.9 +/- 0.19, 1.7 +/- 0.16, and 3.2 +/- 0.70), but the exponential constant k was uninfluenced by growth. Independent of rat size, a 10% increase in loop flow at the midpoint produced at 5-10% decrease in SNGFR. Free-flow values of SNGFR and VLP were found to lie in the most sensitive range of the feedback curve.

The effect of tubular perfusion with PGE2, PGF2α, and PGI2 on the tubuloglomerular feedback control in the rat

1983 ◽  
Vol 61 (11) ◽  
pp. 1317-1323 ◽  
Author(s):  
A. Erik G. Persson ◽  
Bengt Hahne ◽  
Göran Selén
Keyword(s):  
Control Level ◽  
Renal Medulla ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Perfusion Solution ◽  
Sprague Dawley Rats ◽  
Feedback Sensitivity ◽  
Proximal Tubular ◽  
Flow Pressure ◽  
Tubular Flow

The prostaglandins (PG) of the renal medulla might affect the nephron and the cortical arteriolar function via the tubular route. To investigate this question PGE2 (1 μg/mL), PGF2α (10 μg/mL), or PGI2 (1 ng/mL) was added to the tubular perfusion solution when the characteristics of the tubuloglomerular feedback (TGF) control were measured. The experiments were performed on Sprague–Dawley rats. The proximal tubular stop-flow pressure (PSF) was measured upstream to a wax block, while at the same time the distal nephron was perfused with prostaglandin-containing or prostaglandin-free solutions at different flow rates varying from 0 to 50 nL/min. The maximal drop in PSF (ΔPSF) and the tubular flow rate at which 50% of the ΔPSF response was obtained, the turning point (TP), were determined. When PGE2 or PGF2α was added to the tubular perfusion solution in the control animals a significant increase in feedback sensitivity was found. After 10 min of tubular PGI2 perfusion the feedback sensitivity was almost completely abolished, with a ΔPSF of 0.8 mmHg (1 mmHg = 133.322 Pa) (control 8.4 mmHg) and a TP of >40 nL/min (control 22 nL/min). After nephrectomy the feedback sensitivity was reduced, with a ΔPSF of 2.0 mmHg and a TP of >40 nL/min. When PGE2 was added to the tubular perfusion solution in the uninephrectomized animals, the feedback sensitivity was increased to the control level, with a ΔPSF of 8.2 mmHg and a TP of 20.0 nL/min. The results show that PGI2 reduces and PGE2 and PGF2α increase TGF sensitivity when added to the tubular perfusion solution and that the decrease seen after nephrectomy is again reset to the control level by intratubular PGE2 administration.

Reset tubuloglomerular feedback permits and sustains glomerular hyperfunction after extensive renal ablation

1991 ◽  
Vol 260 (3) ◽  
pp. F395-F401 ◽  
Author(s):  
R. Salmond ◽  
F. D. Seney
Keyword(s):  
Fluid Flow ◽  
Proximal Tubule ◽  
Renal Mass ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Renal Ablation ◽  
Single Nephron ◽  
The Difference ◽  
Tubule Fluid

To determine the contribution of the tubuloglomerular feedback (TGF) system to glomerular hyperfunction after extensive loss of renal mass, TGF was assessed in anesthetized Sprague-Dawley rats 7 days after 5/6 reduction of renal mass (2/3 infarction of 1 kidney plus contralateral nephrectomy) or sham surgery. Five-sixths renal ablation significantly increased single-nephron (SN) glomerular filtration rate (GFR) 57%, late proximal tubule fluid flow 58-63%, and maximal proximal tubule stop-flow pressure (PSF) 24%. Despite these increments, 5/6 ablation did not increase TGF activation, as judged by the difference between proximally and distally measured SNGFR values, nor did it affect maximal TGF responses, measured as change in PSF during forward microperfusion of the loop of Henle. However, 5/6 ablation increased the late proximal perfusion rate eliciting half-maximal PSF suppression (V1/2) from 27.3 +/- 1.6 to 45.7 +/- 2.4 nl/min (P less than 0.001), a change closely matching the increment in native late proximal tubule fluid flow from 26.6 +/- 2.2 to 43.8 +/- 2.1 nl/min (P less than 0.001). Unilateral nephrectomy increased V1/2 less dramatically than did 5/6 ablation, thus showing that the effects of renal ablation on TGF are proportional to the degree of ablation. We conclude that extensive renal ablation resets TGF operation in a way that permits and helps sustain glomerular hyperfunction.

Evaluation of prostaglandins as mediators of tubuloglomerular feedback

1988 ◽  
Vol 254 (5) ◽  
pp. F642-F649 ◽  
Author(s):  
M. Franco ◽  
P. D. Bell ◽  
L. G. Navar
Keyword(s):  
Nordihydroguaiaretic Acid ◽  
Tubuloglomerular Feedback ◽  
Hypotonic Solution ◽  
Sprague Dawley ◽  
Lipoxygenase Inhibitor ◽  
Synthesis Inhibitor ◽  
Sprague Dawley Rats ◽  
Rapid Restoration ◽  
Flow Pressure ◽  
Feedback Responses

Orthograde and retrograde microperfusion experiments were conducted in Sprague-Dawley rats to evaluate the participation of vasoconstrictive eicosanoids as mediators of tubuloglomerular feedback (TGF) signals. Retrograde perfusion with 160 microM arachidonic acid (AA) added to a hypotonic solution enhanced the stop-flow pressure (SFP) feedback responses compared with those obtained with the control hypotonic solution (delta SFP, 1.6 +/- 0.4 vs. 10.1 +/- 0.7 mmHg with AA). Blockade of thromboxane A2 (TxA2) with the receptor blocker EP 092 or the synthesis inhibitor UK 38485 did not alter the magnitude of the SFP feedback responses obtained with an isotonic solution. Similarly, nordihydroguaiaretic acid, a lipoxygenase inhibitor, did not alter maximal SFP feedback responses. Although indomethacin (5 mM) did induce attenuated SFP feedback responses (delta SFP, 9.5 +/- 0.7 vs. 0.5 +/- 0.4 mmHg with indomethacin), normal feedback responses were restored within 15-90 s after cessation of indomethacin perfusion. Additionally, SFP feedback responses were not inhibited with 5 mM piroxicam, a different cyclooxygenase inhibitor. These data fail to support a role for either TxA2 or lipoxygenase end products as mediators of TGF signals. The rapid restoration of feedback responses after indomethacin exposure and the lack of blockade with piroxicam suggest that transmission of feedback signals is not dependent on cyclooxygenase products.

A micropuncture study of renal lithium reabsorption: effects of amiloride and furosemide

1992 ◽  
Vol 263 (6) ◽  
pp. F1128-F1133 ◽  
Author(s):  
D. G. Shirley ◽  
S. J. Walter ◽  
B. Sampson
Keyword(s):  
Lithium Concentration ◽  
Quantitative Measure ◽  
Distal Tubule ◽  
Control Group ◽  
Lithium Clearance ◽  
Sprague Dawley ◽  
Water Losses ◽  
Fluid Delivery ◽  
Sprague Dawley Rats ◽  
Micropuncture Study

The validity of the lithium clearance technique as a measure of end-proximal fluid delivery was assessed using micropuncture in sodium-replete, Inactin-anesthetized Sprague-Dawley rats. Three groups of animals were used: controls, amiloride treated, and furosemide treated. Diuretic-induced salt and water losses were replaced. Fractional lithium excretion (FELi) was 0.23 +/- 0.01, 0.24 +/- 0.02, and 0.40 +/- 0.03 in the control, amiloride, and furosemide groups, respectively. In each group, the tubular fluid-to-plasma lithium concentration ratio at the end of the proximal convoluted tubule (PCT) was significantly greater than unity (control, 1.16 +/- 0.03; amiloride, 1.16 +/- 0.02; furosemide, 1.17 +/- 0.02). In the control group, fractional lithium delivery (FDLi) at the late PCT was 0.50 +/- 0.02, while FDLi at the early distal tubule was 0.25 +/- 0.01; the latter did not differ significantly from FDLi at the late distal tubule or from FELi. Values in amiloride-treated rats were almost identical. Furosemide had no effect on FDLi at the late PCT, but raised that at the early distal tubule to 0.37 +/- 0.03. We conclude that 1) lithium reabsorption in the PCT lags slightly behind that of water, 2) substantial furosemide-sensitive lithium reabsorption occurs beyond the PCT, and 3) no significant lithium reabsorption occurs in nephron segments beyond the loop. These findings call into question the use of lithium clearance as a quantitative measure of end-proximal fluid delivery in sodium-replete animals.

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